Thursday, February 28, 2013

Imatinib – Promise of the Patent

Teva Canada Ltd v Novartis AG / imatinib 2013 FC 141, Snider J
            GLEEVEC / imatinib mesylate / 2,093,203

Imatinib has proven to be a revolutionary treatment for chronic myeloid leukemia: “What once was a death sentence has now become a manageable chronic illness with overall survival rates equal to the general population” [71]. The ‘203 patent includes a compound claim to imatinib (Claim 29) and a claim to the use of imatinib for the treatment of tumours (Claim 46, read together with Claim 29) [184]. These were the key claims at issue, and both were held to be valid. (Other important claims included Claim 1, the broadest genus claim, which was held to be invalid, and Claim 5, a sub-genus claim encompassing imatinib, which was held to be valid. A number of other claims to individual compounds were also held to be valid.)

As is now standard with respect to pharmaceutical patents, the main attack on the patent was based on lack of utility [8], and a key argument turned on the promise of the patent. In the end, Snider J construed the promise modestly, in favour of the patentee, but her decision illustrates once again that under the false promise doctrine, validity of a pharmaceutical patent may turn on an extraordinarily fine parsing of the description. Whatever the result, this is problematic, as the description is intended to disclose the invention, not to define it; the false promise doctrine means that the same meticulous care that must be given to every word of the claims, should also be given to every word of the description when drafting a Canadian patent application.

The compounds of the ‘203 patent are selective kinase inhibitors. Kinases catalyze phosphorylation of a protein, and are divided into groups depending on the type of amino acid that they phosphorylate. Of particular interest in this case are kinases known as PKC, PDGF-R and ABL. A mutated form of ABL kinase (BCR-ABL) was known to be associated with chronic myeloid leukemia [54]. PDGF-R is found in connective tissue, and there was reason to believe it could be implicated in different forms of cancer and atherosclerosis [59]. PKC was associated with cell proliferation and so was potentially linked to cancer [60]. Kinase inhibitors, as the name suggests, inhibit the action of kinases and so can affect the related physiological processes. Selective kinase inhibitors inhibit only a particular kinase, and so affect the process associated with that kinase, but not other processes. Selective kinase inhibitors, therefore, may be useful for treating a disease with few side-effects. Imatinib treats chronic myeloid leukemia by acting as a selective inhibitor of BCR-ABL.

Snider J began her utility analysis by affirming the centrality of the promise of the patent doctrine: “The promise of the patent should be determined at the outset of the utility analysis in a purposive manner. If the inventors do state a specific promise in the patent, the court must evaluate utility against this promise. Just a mere scintilla of utility is insufficient in the face of a specific promise that requires more” [166, citations omitted], and finally, “Utility must be assessed against the promise of the '203 Patent” [169]. That this last statement should seem unremarkable illustrates the sea change in Canadian utility law over the past decade. Formally, “[w]here the specification does not promise a specific result, no particular level of utility is required; a ‘mere scintilla’ of utility will suffice. However, where the specification sets out an explicit ‘promise’, utility will be measured against that promise” Lilly / olanzapine (No 1) 2010 FCA 197 [76]. In practice, as Snider J’s review of the law indicates, the requirement that the promise be “explicit” is broadly interpreted, so that the courts have invariably been able to find some wording in the description that might be construed as a promise. Nor is there ever any consideration of whether this promise is material to grant, as was originally required: “If [the patent] be avoided it can only be because it contains a misrepresentation so material that it can be said the Crown has been deceived.” Alsop’s Patent (1907), 24 RPC 733, 753 (Ch). I argue in a forthcoming article that the false promise doctrine developed as a reflection of the discretionary nature of the patent grant in UK law, and it is inconsistent with the Canadian Patent Act in which there is no discretion to refuse a patent for an invention which meets the statutory requirements. But even if we accept the doctrine, the holding that utility must be assessed against the promise of the patent, which abandons the requirement of an explicit material promise, shows that Canadian law has moved well beyond its English antecedents. (This is not particularly a criticism of this statement by Snider J, which is merely an explicit recognition of the now-established practice.)

Turning to the details, the evidence showed, and indeed it was conceded that, imatinib showed in vitro activity against ABL kinase [196,245]. If such activity was sufficient to establish utility, as Novartis argued, the patent was clearly useful. Consequently, in order to attack the utility of the patent, the plaintiffs argued that the patent promised in vivo therapeutical effect in treating cancer associated with both PDGF-R and ABL [170].

The first dispute in the construction of the promise was the so-called “and/or” issue [120ff]. The description grouped the disclosed compounds into three groups, referred to as Group 1, Group 1A and Group 2, and it stated that [123-24, Snider J’s emphasis]

[The Group 1A compounds] inhibit not only protein kinase C but . . . also certain tyrosine kinases, such as especially PDGF-receptor kinase or abl-kinase. . . . [Group 2 compounds] are especially selective for the above-mentioned PDGF-receptor and abl-tyrosine kinases and inhibit kinase C virtually not at all.

The plaintiffs argued that the use of “or” in one sentence, and “and” in a parallel sentence in the same paragraph showed an intent to differentiate these terms, so that the second sentence should be read as promising that Group 2 compounds, including imatinib, would inhibit both PDGF-R and ABL, not merely one or the other. Snider J rejected this argument, stating that “The English word ‘and’ is notoriously ambiguous,” and read in context, the focus of the sentences is to contrast the effect on PKC: what the paragraph really says is that Group 1A compounds inhibit PKC, while Group 2 compounds do not [128]. Snider J distinguished her own prior decision in Desloratadine (NOC)2009 FC 1128, which in effect interpreted “or” to mean“both,” on the basis that the expert evidence as to the meaning of the term was different in the two cases [135-37].

The second dispute was over the meaning of the words “can be used,” and particularly whether “can” implied mere possibility, or near certainty, of use for the specified purposes [143]. Expert evidence conflicted, and Snider J pointed out that as a matter of ordinary usage, “can” is reasonably capable of bearing either interpretation [146]. She distinguished the decision of Boivin J in Clopidogrel 2011 FC 1486 essentially on the basis that interpretation of a term in the disclosure requires a holistic assessment of the record, and so the interpretation of a word in one case is not binding in another case, and is not even persuasive authority [148]. Snider J concluded that in this context “can” meant “potential,” though she pointed to little that was specifically in support of this conclusion. She did contrast the phrase “have valuable pharmacological properties,” which she took to suggest “almost [a] guarantee,” with “can be used” which she took to imply less certainty [150]. That is, “have” implies more certainty than “can.” I must say that I do not find this point very persuasive. I would have thought a compound “has” valuable pharmacological properties even if it only has the potential to be a miracle cure for a certain type of cancer.

To my mind, Snider J’s interpretation of these phrases are entirely reasonable, but the opposite interpretation would also have been reasonable. I remark in my forthcoming False Promise article that “The cases . . .illustrate that the construction of the promise of the patent, and consequently the validity of the claims, may turn on what might fairly be called a ‘hair-splitting’ interpretation of the words of the specification which recalls the ‘meticulous verbal analysis’ of the type disparaged in Catnic.” Snider J’s analysis in this case confirms this observation. It is shocking that the validity of a patent that has transformed the lives of cancer sufferers might turn on the interpretation of a “notoriously ambiguous” word. As a matter of principle, Snider J was right to distinguish other cases dealing with similar terms on their facts, but this serves to further emphasize the arbitrariness of the exercise of construing the patent. Again, this is not intended as a criticism of Snider J’s analysis or conclusions, which I think are perfectly reasonable. The problem lies with the false promise doctrine itself, which mandates this kind of analysis.

After construing the promise of the patent in favour of the patentee, Snider J held all of the compound claims, including Claim 29 to imatinib, to be useful on the basis of demonstrated utility [245, 247]. I should note that the “and/or” debate was not determinative of validity, because on the facts Snider J found that imatinib did selectively inhibit both PDGF-R and ABL kinases [246], though the evidence regarding ABL kinases was more direct [245]. That the more stringent promise was satisfied on the facts does not change the point that such a fine distinction could potentially determine the validity of the patent.

At the outset of her construction of the patent, Snider J quoted Justice Dickson in Consolboard [1981] 1 SCR 504 at 520, as saying that “There is no occasion for being too astute or technical in the matter of objections to either title or specification for . . . the patent should be approached ‘with a judicial anxiety to support a really useful invention’.” [74, Snider J’s emphasis.] Later, she quoted the FCA approving Zinn J’s statement that “the jurisprudence does not permit an unescorted and unchaperoned romp through the disclosure” [168, quoting 2012 FCA 103 [57]]. These statements provide a principled basis for reining in the promise of the patent doctrine. Though she did not specifically invoke Consolboard in construing “and/or” and “can be used,” Dickson J’s dictum would justify Snider J’s choice of a construction favouring the patentee on these points, given that the words could reasonably bear either interpretation, While sound in principle, this type of restrained interpretation is a treatment, rather than a cure, for the false promise doctrine.

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